To Evaluate the Role of Antibiotic (Gramicidin A) in Myeloid Leukemia

Abstract

Gramicidin A is a well-known antibiotic and recently was reported to induced tumour cell death, however, little is understood about the molecular mechanism of gramicidin A as a therapeutic agent for solid tumours. Similarly, its role in liquid cancer is unknown.Here, we investigated the role of gramicidin A in leukemic cells. Leukemia is the cancer of white blood cells and is of two origin i-e myeloid and lymphoid origin. Gramicidin A upon testing in vitro interferes with the proliferation potential of PML/RARα-positive APL cells and BCR-ABL positive CML cells. The current study evaluated the cell cytotoxicity of gramicidin A and its anti proliferative activity on NB4 and K562 cell lines. Generalized toxicity is a significant challenge to the development of ionophores as therapies for human cancer. But we identified a concentration of Gramicidin A showing no hemolysis. Furthermore, we investigated the combine effect of already approved treatments of CML and APL with Gramicidin A and is has shown additive effect in both cases. Similarly, the expression analysis indicated that Gramicidin A interferes with the β-catenin dependent leukemogenesis and downregulates AXL-RTK in APL cells with the expected downregulation of downstream c-Myc, Eya3 and Axin 2 related to the Wnt/β-catenin signalling. Taken together, these results demonstrate a new role for gramicidin A as a potent inhibitor in case of myeloid leukemia.